Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 21, 2025; 31(11): 100785
Published online Mar 21, 2025. doi: 10.3748/wjg.v31.i11.100785
NAD+/SIRT1 pathway regulates glycolysis to promote oxaliplatin resistance in colorectal cancer
Ya-Ru Niu, Mi-Dan Xiang, Wen-Wei Yang, Yu-Ting Fang, Hai-Li Qian, Yong-Kun Sun
Ya-Ru Niu, Mi-Dan Xiang, Wen-Wei Yang, Yu-Ting Fang, Yong-Kun Sun, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
Hai-Li Qian, National Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
Co-first authors: Ya-Ru Niu and Mi-Dan Xiang.
Author contributions: Qian HL and Sun YK conceived the project and provided funding support for the experiments; Niu YR designed the study, performed the experiments and wrote the manuscript; Xiang MD collected the data and performed the data analysis; Yang WW and Fang YT assisted with data analysis and provided critical revisions; All the authors reviewed and approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 82072756; and Beijing Xisike Clinical Oncology Research Foundation, No. Y-HR2019-0285.
Institutional animal care and use committee statement: All animal experiments were approved by the Animal Control Committee of the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital of the Chinese Academy of Medical Sciences and Peking Union Medical College (NCC2024A242).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: The relevant research data are included in the manuscript. Additional data will be made available upon request at hsunyk@cicams.ac.cn.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yong-Kun Sun, PhD, Chief Doctor, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuan Nanli, Chaoyang District, Beijing 100021, China. hsunyk@cicams.ac.cn
Received: August 27, 2024
Revised: December 13, 2024
Accepted: February 13, 2025
Published online: March 21, 2025
Processing time: 199 Days and 1.1 Hours
Core Tip

Core Tip: SIRT1, a NAD+-dependent deacetylase, has demonstrated anti-tumor effects in numerous studies. However, the role of SIRT1 in regulating oxaliplatin resistance remains unclear. This study found that SIRT1 expression is downregulated in oxaliplatin-resistant colorectal cancer (CRC) cell. Enhancing SIRT1 expression reverses this resistance. Mechanistically, DNA damage-induced PARP activation inhibits SIRT1 expression. The inhibition of SIRT1 promotes drug resistance in CRC cells by enhancing glycolysis. These findings highlight the critical role of SIRT1 in oxaliplatin resistance and support the potential of combining SIRT1 agonists with oxaliplatin as a therapeutic strategy to overcome CRC resistance.